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Infection and Immunity, November 2005, p. 7304-7310, Vol. 73, No. 11
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.11.7304-7310.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Cell-Mediated Protection against Pulmonary Yersinia pestis Infection

Michelle A. Parent, Kiera N. Berggren, Lawrence W. Kummer, Lindsey B. Wilhelm, Frank M. Szaba, Isis K. Mullarky, and Stephen T. Smiley*

Trudeau Institute, Saranac Lake, New York

Received 2 June 2005/ Returned for modification 14 July 2005/ Accepted 18 July 2005

Pulmonary infection with the bacterium Yersinia pestis causes pneumonic plague, an often-fatal disease for which no vaccine is presently available. Antibody-mediated humoral immunity can protect mice against pulmonary Y. pestis infection, an experimental model of pneumonic plague. Little is known about the protective efficacy of cellular immunity. We investigated the cellular immune response to Y. pestis in B-cell-deficient µMT mice, which lack the capacity to generate antibody responses. To effectively prime pulmonary cellular immunity, we intranasally vaccinated µMT mice with live replicating Y. pestis. Vaccination dramatically increased survival of µMT mice challenged intranasally with a lethal Y. pestis dose and significantly reduced bacterial growth in pulmonary, splenic, and hepatic tissues. Vaccination also increased numbers of pulmonary T cells, and administration of T-cell-depleting monoclonal antibodies at the time of challenge abrogated vaccine-induced survival. Moreover, the transfer of Y. pestis-primed T cells to naive µMT mice protected against lethal intranasal challenge. These findings establish that vaccine-primed cellular immunity can protect against pulmonary Y. pestis infection and suggest that vaccines promoting both humoral and cellular immunity will most effectively combat pneumonic plague.

* Corresponding author. Mailing address: Trudeau Institute, 154 Algonquin Avenue, Saranac Lake, NY 12983. Phone: (518) 891-3080. Fax: (518) 891-5126. E-mail: ssmiley{at}trudeauinstitute.org.

Editor: D. L. Burns

Infection and Immunity, November 2005, p. 7304-7310, Vol. 73, No. 11
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.11.7304-7310.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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